Redox properties of the adenoside triphosphate-sensitive K+ channel in brain mitochondria

Brain mitochondrial ATP-sensitive K+ channel (mito-K-ATP) opening by diazoxide protects against ischemic damage and excitotoxic cell death. Here we studied the redox properties of brain mito-K-ATP. Mito-K-ATP activation during excitotoxicity in cultured cerebellar granule neurons prevented the accumulation of reactive oxygen species (ROS) and cell death. Furthermore, mito-K-ATP activation in isolated brain mitochondria significantly prevented H2O2 release by these organelles but did not change Ca2+ accumulation capacity. Interestingly, the activity of mito-K-ATP was highly dependent on redox state. The thiol reductant mercaptopropionylglycine prevented mito-K-ATP activity, whereas exogenous ROS activated the channel. In addition, the use of mitochondrial substrates that led to higher levels of endogenous mitochondrial ROS release closely correlated with enhanced K+ transport activity through mito-K-ATP. Altogether, our results indicate that brain mito-K-ATP is a redox-sensitive channel that controls mitochondrial ROS release. (c) 2008 Wiley-Liss, Inc.